Corneal nerve fibers exert trophic effects on the corneal epithelium, regulate epithelial ion transport processes, and influence epithelial mitogenesis and corneal wound healing. The mechanism by which corneal innervation exerts these influences is unknown, but axonally transported substances, possibly neuropeptides, may be involved. The aims of the current study are to investigate in detail the origins, density, fine structure, and neuropeptide content of the corneal sensory and sympathetic innervations, and to investigate the role of corneal neuropeptides on epithelial mitogenesis and corneal wound healing. Eight types of experiments will be performed in the current study. First, the distribution, numbers, and somata diameters of corneal afferent and efferent neurons in 5 different species will be investigated by the method o? retrograde transport of horseradi peroxidase-wheat germ agglutinin (HRP-WGA). Second, the fine structure and postsynaptic relationships of rat corneal sensory fibers, and rabbit and cat sympathetic fibers, will be studied at the electron microscopic level by labeling the fibers with HRP-WGA transported anterogradely from the trigeminal and superior cervical ganglia. Third the overall densities of the corneal adrenergic Innervations in 5 species will be determined by applying glyoxylic acid-induced fluorescence techniques to the study of split corneal whole mount preparations- Fourth, the brainstem termination sites of rabbit corneal afferent neurons will be investigated by using the method of transganglionic transport of HRP-WGA. In the fifth and sixth sets of experiments, the neuropeptide content of the rat and rabbit corneal innervation will be studied by using immunohistochemical techniques designed to detect the presence of substance P, calcitonin gene-related peptide, cholecystokinin, somatostatin, leucine enkephalin, and neuropeptide Y. In the seventh se of experiments, we will test the ability o? topically applied neuropeptides to alter the rate of epithelial mitogenesis and, in the final set of experiments, we will study the wound healing potential of different neuropeptides or combinations of neuropeptides on three kinds of: standardized, non-penetrating corneal lesions. The long term objectives of the current application are to increase our understanding of the efferent (nonsensory) functions o? the corneal innervations, and to learn if biologically active substances produced and transported in corneal nerves may be used therapeutically to stimulate corneal repair following eye injuries and, perhaps, corneal transplantations.